TWI826527B - Crystalline mixture of bisfluorene compounds - Google Patents

Abstract

An objective of the present invention is to provide a crystalline mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl] fluorene having a specific endothermic peak by differential scanning calorimetry, and a method for producing the crystalline mixture. As a solving means, the present invention provides a crystalline mixture of 9,9-bis [4-(2-hydroxyethoxy)-3-phenylphenyl] fluorine, the crystalline mixture has at least one endothermic peak by differential scanning calorimetry in a temperature range from 157 ℃ or higher and 163 ℃ or lower, furthermore, it has at least one endothermic peak in the temperature range of 176 ℃ or higher and 179 ℃ or lower.

Description

Crystalline mixture of bisfluoride compounds

The present invention relates to a crystal mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride having a specific endothermic peak measured by differential scanning calorimetry and the crystal Methods of making hybrids.

In the past, a group of compounds with a fluorine skeleton such as 9,9-bis(4-hydroxyphenyl)fluoride have been used in thermoplastic synthetic resin raw materials such as polycarbonate resin and epoxy resin because of their excellent heat resistance and optical properties. Such as thermosetting resin raw materials, antioxidant raw materials, thermal recording material raw materials, photoresist raw materials, etc. Among them, the resin produced from 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride having the chemical structure represented by the following chemical formula (1) has excellent optical properties. and attracted attention (for example, Patent Documents 1 and 2, etc.).

It is known that a method for producing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride represented by the above chemical formula (1) is as shown in the following reaction formula: 9-Fundone represented by chemical formula (2) A method for obtaining the target product by reacting with alcohols represented by chemical formula (3) (Patent Document 3).

In addition, it is known that aromatic hydrocarbons and methanol are added to a reaction liquid containing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride represented by the above chemical formula (1). , and after separating the precipitated crystals, the method is to remove methanol by making the crystals reach a temperature of 60°C or higher (Patent Document 4). The crystal obtained by crystallization is an inclusion compound (inclusion compound, also called clathrate compound) of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride and methanol. ), in order to remove the included methanol, energy and time caused by heating are indispensable.

A known method for removing toluene is by not combining 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorine represented by the above chemical formula (1) with toluene. The compound and a specific solvent are dissolved and mixed to remove toluene (Patent Document 5). However, since most of the crystals obtained have high melting points, it takes a lot of energy and time to melt or dissolve the crystals. . In addition, although a low-melting-point crystal can be obtained by using a solvent, since the crystal forms a clathrate, not only does it consume energy to remove the solvent from the clathrate, but the bulk density also increases. Low.

A method for producing a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride represented by the above chemical formula (1) with a high overall density is known (Patent Document 6) , however, the obtained crystal is a clathrate, and the solvent cannot be removed from the clathrate by heating while maintaining the original crystalline state, or even if the solvent can be removed, energy is required. Coming general The problem of solvent removal from inclusion compounds.

A method for producing 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride represented by the above chemical formula (1) that is not a clathrate is also known (Patent Document 7 ), but the crystal with the highest melting point requires a lot of energy to be melted and used. In addition, in order to obtain low melting point crystals, it is necessary to cool at an extremely fast speed, which is difficult to implement on a commercial scale, or requires the use of special equipment, so it is not easy to apply on an industrial scale. In addition, the low-melting point crystal has a different hue, which causes problems in its use for optical purposes. There is also a problem that a large amount of the solvent used for crystallization remains.

It is known that a group of compounds having a fluorine skeleton, such as 9,9-bis(4-hydroxyphenyl)benzoate, form inclusion complexes with the reaction solvent or the solvent used for purification. This is because it is necessary to remove the included solvent. It is high temperature and takes a lot of time, so it is difficult to apply it on an industrial scale. In addition, it is also known that compounds with a fluorine skeleton containing a solvent are used as raw materials for the production of epoxy resins, polyesters, etc. and for other uses. There are problems with industrial use.

[Prior technical literature] [Patent Document]

Patent Document 1: Japanese Patent Application Publication No. 2001-074222

Patent Document 2: Japanese Patent Application Publication No. 2011-168722

Patent Document 3: Japanese Patent Application Publication No. 2001-206863

Patent Document 4: Japanese Patent Application Publication No. 2017-200900

Patent Document 5: Japanese Patent Application Publication No. 2018-076245

Patent Document 6: Chinese Patent Application Publication No. 106349030 Specification

Patent Document 7: Japanese Patent Application Publication No. 2017-200901

The present invention was made in view of the above background, and its object is to provide a crystal mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride and the crystal mixture. A method for manufacturing a body wherein the aforementioned crystalline mixture has a specific endothermic spectrum peak measured based on differential scanning calorimetry.

The inventors of the present invention conducted intensive studies to solve the above-mentioned problems and found that by using a specific solvent for crystallization, 9,9-bis[4-(( A crystalline mixture of 2-hydroxyethoxy)-3-phenylphenyl]fluorine completes the present invention.

The present invention is described below.

1. A crystalline mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride, which has at least 1 basis in the temperature range of 157°C above and 163°C below Endothermic peaks measured by differential scanning calorimetry, and having at least one endothermic peak in the temperature range above 176°C and below 179°C.

2. The crystal mixture according to 1., wherein each of the crystal mixture is not a clathrate.

3. The crystal mixture as described in 1., in the powder X-ray diffraction pattern obtained by using Cu-Kα rays, the diffraction angles 2θ=7.5±0.2°, 11.1±0.2°, 17.6±0.2°, Those with spectral peaks at 19.1±0.2°, 20.5±0.2° and 21.1±0.2°.

4. A method for producing the crystal mixture according to any one of 1. to 3., which includes the step of crystallizing using a mixed solvent of acetone and water.

5. The manufacturing method as described in 4., further comprising: drying the crystals obtained by crystallization at a temperature of 45° C. or higher and lower than the melting point.

According to the present invention, a crystal mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride and a method for producing the crystal mixture can be provided, wherein the crystal mixture has Based on the specific endothermic peak measured by differential scanning calorimetry, it is not an inclusion compound.

In the case where 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride is included with a compound such as an organic solvent, when the inclusion compound is mixed with, for example, (meth)acrylic acid When the reaction is carried out, there will be a problem that the included organic solvent and other compounds hinder the reaction and make the reaction impossible. Furthermore, when the clathrate is melted and used as a resin raw material, in addition to the vapor derived from the "compounds such as included organic solvents" generated during the melting, it is necessary to remove from the reaction device, as well as The quality of the target resin is reduced due to residual organic solvents and other compounds. In addition, depending on the flash point and ignition point of compounds such as organic solvents included, there may be disaster prevention concerns during the transportation and storage of the inclusion compounds.

As mentioned above, there is no known so-called "crystalline mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride having properties based on differential scanning calorimetry" Determination It has a specific endothermic peak, and the crystal is not an inclusion compound." Furthermore, compared with conventional methods for removing organic solvents from clathrates, in most cases the contained organic solvent can be removed with much lower heat, so the energy consumed during production can be suppressed. Furthermore, compared with high-melting-point crystals that are not clathrates, the crystals can be melted or dissolved at a lower temperature or in a shorter time, so in this regard, the energy consumed during manufacturing can also be reduced.

That is, "a 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride that has a specific endothermic peak measured based on differential scanning calorimetry and is not an inclusion compound. The provision of "novel crystalline mixture" and its manufacturing method is very useful for industrial use such as resin raw materials.

Figure 1 is a graph showing a differential thermogravimetry (DTG: Differential Thermogravimetry) curve of the crystal obtained in the reference example.

Figure 2 is a graph showing a differential scanning calorimetry (DSC: Differential Scanning Calorimetry) curve of the crystal mixture obtained by the drying step of Example 1 (crystal mixture of the present invention).

Figure 3 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal mixture obtained by the drying step of Example 1 (crystal mixture of the present invention).

Fig. 4 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve for calorimetry in which acetone is removed from the acetone clathrate obtained by the crystallization step of Example 1.

Figure 5 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained by the crystallization step of Example 2.

Figure 6 is a graph showing a differential scanning calorimetry (DSC) curve of the crystal mixture obtained by the drying step of Example 2 (crystal mixture of the present invention).

Figure 7 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained by the crystallization step of Example 3.

Figure 8 is a graph showing a differential scanning calorimetry (DSC) curve of the crystal mixture obtained by the drying step of Example 3 (crystal mixture of the present invention).

Figure 9 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 2.

Figure 10 is a graph showing a differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 3.

Figure 11 is a graph showing a differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 4.

Figure 12 is a graph showing a differential scanning calorimetry (DSC) curve of the crystal obtained in Comparative Example 5.

Figure 13 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 6.

Figure 14 is a graph showing a differential thermal/thermogravimetric analysis (DTG) curve of the crystal obtained in Comparative Example 8.

Figure 15 shows differential thermal/thermogravimetric analysis of crystals before drying in Comparative Example 9. (DTG) curve graph.

Figure 16 is a graph showing a differential scanning calorimetry (DSC) curve of the dried crystal of Comparative Example 9.

The present invention will be described in detail below.

9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride of the present invention is a compound represented by the following chemical formula (1).

<resolve resolution>

The synthesis method of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride of the present invention is not particularly limited. For example, the known production method described in the aforementioned Patent Document 3 can be applied. .

Describe the reaction between 9-quinone represented by the chemical formula (2) and the alcohol represented by the chemical formula (3) shown in the following reaction formula.

The molar ratio of the alcohol represented by the chemical formula (3) to the 9-quinone represented by the chemical formula (2) is not particularly limited as long as it is above the theoretical value (2.0). Usually, 2 to 20 times the molar ratio is used. quantity The range is preferably 3 to 10 times the molar amount.

An acid catalyst can be used during the reaction. The acid catalyst used is not particularly limited, and known acid catalysts can be used. Examples of specific acid catalyst systems include: hydrochloric acid, hydrogen chloride gas, 60 to 98% sulfuric acid, 85% phosphoric acid and other inorganic acids; p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, formic acid, trichloroacetic acid or trifluoroacetic acid, etc. Organic acids; solid acids such as heteropoly acid (heteropoly acid), etc. Preferred are heterogeneous polymeric acids such as phosphotungstic acid. The appropriate usage amount of such an acid catalyst will vary depending on the reaction conditions. For example, in the case of heterogeneous polymeric acids such as phosphotungstic acid, it can be 1 to 70 parts by weight relative to 100 parts by weight of 9-quinone. The range is preferably 5 to 40 parts by weight, and more preferably 10 to 30 parts by weight.

During the reaction, acid catalysts and catalyst accelerators such as mercaptans may also be used simultaneously if necessary. By using it in this way, the reaction speed can be accelerated. Examples of such thiols include alkyl mercaptans and mercaptocarboxylic acids. Preferred are alkyl mercaptans having 1 to 12 carbon atoms and mercaptocarboxylic acids having 1 to 12 carbon atoms. Examples of alkyl mercaptans having 1 to 12 carbon atoms include methyl mercaptan, ethyl mercaptan, n-octyl mercaptan, n-dodecyl mercaptan, and bases such as sodium salts thereof. Examples of metal salts and mercaptocarboxylic acids having 1 to 12 carbon atoms include thioacetic acid, β-mercaptopropionic acid, and the like. Moreover, these can be used individually or in combination of 2 or more types. The amount of thiols used as a catalyst accelerator is usually in the range of 1 to 30 mol%, preferably in the range of 2 to 10 mol%, relative to the raw material 9-quinone.

During the reaction, the reaction solvent may not be used, or it may be used for reasons such as improved operability and reaction speed during industrial production. As for the reaction solvent, there are no special restrictions as long as it does not distill out from the reactor at the reaction temperature and is inactive for the reaction. Examples include: aromatic hydrocarbons such as toluene and xylene; lower aliphatic alcohols such as methanol, ethanol, 1-propanol, and 2-propanol; saturated aliphatic hydrocarbons such as hexane, heptane, and cyclohexane, and other organic Solvent and water or mixtures thereof. Among these, aromatic hydrocarbons are preferably used.

The reaction temperature varies depending on the type of acid catalyst used. When using anisotropic polymeric acid such as phosphotungstic acid as the acid catalyst, the reaction temperature is usually 20 to 200°C, preferably 40 to 170°C, more preferably 40 to 170°C. The preferred range is 50 to 120°C. The reaction pressure can be carried out under increased pressure or reduced pressure so that the reaction temperature is within the aforementioned range according to the boiling point of the organic solvent used, or the reaction can be carried out while removing the generated water.

The reaction time varies depending on the type of acid catalyst used and reaction temperature and other reaction conditions, but usually ends in about 1 to 30 hours.

The end point of the reaction can be confirmed by liquid chromatography or gas chromatography analysis. Preferably, the time point when it is confirmed that the unreacted 9-quinone has disappeared and no further increase in the target substance is observed is set as the end point of the reaction.

〈About post-processing of the reaction〉

After the reaction is completed, known post-treatment methods can be applied. For example, in order to neutralize the acid catalyst, an alkali aqueous solution such as a sodium hydroxide aqueous solution or an ammonia aqueous solution is added to the reaction completion liquid. The neutralized reaction mixture is allowed to stand, and if necessary, a solvent for separation from water is added to separate and remove the water layer. If necessary, perform the operation of "adding distilled water to the obtained oil layer, stirring and washing with water, and then separating and removing the water layer" once or multiple times to remove the neutralizing salt, and directly cool the obtained oil layer and Precipitate crystals, you can separate the precipitated crystallize to obtain crude crystals. In addition, the remaining solvent and the alcohol represented by the above chemical formula (3) can also be removed from the obtained oil layer by distillation, and a solvent such as aromatic hydrocarbons can be added to the obtained residue to prepare a uniform solution. , the crystals precipitated by cooling are separated to obtain crude crystals. This crude crystal and the aforementioned residue can be subjected to the crystallization step of the present invention to obtain a crystal mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorine. It has a specific endothermic peak measured by differential scanning calorimetry and is not an inclusion compound.

〈About the crystallization step〉

The manufacturing method of the present invention includes the step of crystallizing using a mixed solvent of acetone and water. Among them, the acetone that can be used is not particularly limited, and generally commercially available acetone can be used. Furthermore, the water that can be used is not particularly limited, and for example, tap water, distilled water, ion exchange water, natural water, etc. can be suitably used.

For a mixed solvent of acetone and water, the acetone concentration is preferably 55 to 80% by weight, more preferably 60 to 70% by weight. When the water content is extremely small, 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride used for crystallization contains a large amount of reaction or post-reaction treatment. In the case of using a solvent (for example, an aromatic hydrocarbon solvent such as toluene), the possibility that the crystal obtained by crystallization will form a clathrate with the solvent increases, so this is undesirable. In addition, when the water content is extremely high, the possibility that the crystal obtained by crystallization will become a clathrate that requires a large amount of heat to remove the solvent is increased, which is undesirable.

100 parts by weight of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorine contained in the residue or crude crystal obtained from the reaction post-treatment step used in the crystallization step , used The amount of the mixed solvent of acetone and water is preferably 100 to 1000 parts by weight, more preferably 150 to 700 parts by weight, and even more preferably 200 to 600 parts by weight. When the amount of the mixed solvent of acetone and water is large, the amount of crystals obtained will be reduced. When the amount of the mixed solvent of acetone and water is small, the purity of the target product will be reduced, which is unfavorable.

Furthermore, as shown in the reference examples below, it was confirmed that 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl is not a inclusion compound if the residual solvent is 1% by weight or less. ], even if only acetone is used as the crystallization solvent, the crystal mixture of the present invention can be obtained.

In the crystallization step of the present invention, a mixed solvent of acetone and water can be added to the residue or crude crystal after the reaction post-treatment step to achieve the above-mentioned mixing ratio (weight ratio) of acetone and water, and the mixture can be placed under normal pressure. Or, it can be heated under pressure to below the boiling point of the mixed solvent to completely dissolve it and form a uniform solution, and then cool it to obtain precipitated crystals. After heating to form a uniform solution, cooling is performed at 1 to 10°C per hour, preferably at 3 to 8°C. The temperature for crystallization is preferably 40°C or higher, more preferably 50°C or higher. In addition, a seed crystal can be used when crystallizing. Examples of seed crystals used include 9,9-bis[4-(2-hydroxyethoxy)-3-benzene that is not a clathrate and has a residual solvent of 1% by weight or less as shown in the reference examples below. phenyl]fluoride, and crystals obtained by crystallization from acetone, etc. In order to obtain seed crystals, the residual solvent of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride is preferably 0.5% by weight or less, and 0.3% by weight is preferred. % or less is more preferred, and 0.1% by weight or less is particularly preferred. Such 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride can also be produced by, for example, the method described in the above-mentioned Document 4, or by heating a known toluene clathrate. Obtained by melting to remove the solvent, as long as it is analyzed by high-speed liquid chromatography If the obtained purity is approximately 90% or more, preferably 95% or more, either crystalline or amorphous may be used. After the crystallization starts, it is advisable to maintain the crystallization temperature for about 0.1 to 1 hour, preferably about 0.4 to 0.6 hours. Then, it is advisable to cool to 0 to 40°C, preferably 10 to 35°C, and more preferably 20 to 30°C at a cooling rate of 1 to 10°C per hour, preferably 3 to 8°C, and filter through Wait to separate the precipitated crystals. In addition, acetone can also be added to the residue or crude crystal after the reaction post-treatment step, and the solution can be completely dissolved to form a uniform solution, and stirred to achieve the above-mentioned mixing ratio (weight ratio) of acetone and water. Water is added dropwise to obtain precipitated crystals. In this case, it is preferable to maintain a temperature of 50°C or above during crystallization, more preferably to maintain the same temperature for at least 1 hour or more from the start of crystallization, and then further cool to 0 to 60°C, preferably 10 to 10°C. 50°C, preferably 20 to 40°C, and separate the precipitated crystals. The crystal used in the crystallization step of the present invention is preferably a crystal of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorine containing an aromatic hydrocarbon solvent such as toluene. Through the crystallization step of the present invention, the clathrate formed with the aromatic hydrocarbon solvent is converted into a clathrate formed with acetone, etc., which can remove the organic solvent at a temperature lower than the melting point of the clathrate. Conventional inclusion compounds of solvents can remove included solvents such as acetone with much lower heat than the previous ones.

〈About the drying step〉

By performing the drying step, the solvent (acetone, water) used in the crystallization step of the present invention can be removed. The drying step of the present invention can be carried out at a temperature of 45°C or above and lower than the melting point of the crystals obtained by the crystallization step, preferably 70°C or above, and more preferably 90°C. ℃ or above, particularly preferably above 100 ℃. Furthermore, depending on other conditions, etc., the hue of the crystal may be deteriorated by heat, so the temperature is preferably 150°C or lower, and more preferably 130°C or lower. At a temperature lower than 45°C, the solvent (acetone, water) used in the crystallization step cannot be removed, or even if it can be removed, it will take a lot of time, which is not good.

When the drying step is carried out, it can be carried out under normal pressure or under reduced pressure. However, when carried out industrially, the solvent (acetone, acetone, etc.) used in the crystallization step can be removed more efficiently when carried out under reduced pressure. water), so it is also suitable. In addition, the drying step is preferably carried out in an inert gas environment such as nitrogen.

〈Crystal mixture of the present invention〉

The crystallization mixed system of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride of the present invention has at least one basis for differential scanning in the temperature range of above 157°C and below 163°C. The endothermic peak measured by thermal analysis, and having at least one endothermic peak in the temperature range above 176°C and below 179°C. According to the endothermic peak measured by differential scanning calorimetry, the temperature range of the endothermic peak is preferably between 159°C and below 163°C, and the temperature range between 160°C and below 163°C is even better, and the temperature range is above 160°C. The temperature range below 162.5℃ is particularly good. In addition, the temperature range for one endothermic spectrum peak measured by differential scanning calorimetry is more preferably 176°C or more and 178°C or less, and it is still more preferably the temperature range is 176°C or more and 177°C or less.

Furthermore, the crystal mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride of the present invention is not a inclusion compound, that is, it does not include organic solvents, etc. A crystalline mixture of compounds. In the present invention, the so-called crystal mixture that does not contain compounds such as organic solvents is preferably a crystal mixture with a residual organic solvent content of 1 wt% or less, and more preferably a crystal mixture with a residual organic solvent content of 0.5 wt% or less. , and more preferably, a crystalline mixture with a content of less than 0.3% by weight.

[Example]

The following examples are used to illustrate the present invention in more detail, but the present invention is not limited to these examples.

The analysis method is described below.

<Analytical method>

1. Differential scanning calorimetry (DSC)

5 mg of the crystal mixture was weighed into an aluminum pan and measured under the following operating conditions using a differential scanning calorimeter (DSC-60 manufactured by Shimadzu Corporation) using alumina as a control.

(Operating conditions)

Heating rate: 10℃/min

Measuring temperature range: 30 to 200℃

Measuring ambient gas: open, nitrogen 50mL/min

2. Differential thermal/thermogravimetric analysis (DTG)

8 mg of the crystal mixture was weighed into an aluminum pan, and measured under the following operating conditions using a differential heat/thermogravimetric analyzer (manufactured by Shimadzu Corporation: TG-60A).

(Operating conditions)

Heating rate: 10℃/min

Measuring temperature range: 30 to 300℃

Measuring ambient gas: open, nitrogen 50mL/min

3.HS-GC (residual solvent determination)

"HS-GC" refers to a method in which the gas phase part (headspace, HS (headspace)) is introduced into gas chromatography (GC) for analysis. The sample sealed in a vial is kept warm for a certain period of time to allow the gas phase and the sample to reach equilibrium. The gas phase part is analyzed to measure the amount of solvent remaining in the crystal. Specifically, 0.5 g of the crystal mixture was weighed, and N-methylpyrrolidone was added to the crystal mixture while weighing it accurately so that the total amount would be 10 g. Weigh approximately 3 g of this solution into a vial for HS, clamp it tightly to prevent leakage, and measure under the following conditions.

(GC analysis conditions)

Device: Shimadzu Manufacturing Co., Ltd. Manufacture: GC-2010plus

Column: TC-1 60m×0.25mmΦ, film thickness 0.25μm

Detector: FID

INJ temperature: 300℃, FID temperature: 310℃

Heating conditions: 40℃ (25 minutes) → 20℃/min → 300℃ (5 minutes)

Pipe column linear speed: 19.9cm/second

(HS analysis conditions)

Machine: TurboMatrix HS 40 (Perkin Elmer Company)

Carrier gas pressure: 154kPa

Vial heating temperature: 100℃

Injection time: 0.05 minutes

4. Powder X-ray diffraction (XRD: X-ray Diffraction) analysis

0.1 g of the crystal was filled in the sample filling part of the glass test plate, and the following powder X-ray diffraction apparatus was used and the measurement was performed under the following conditions.

Device: Rigaku Co., Ltd. Manufacturer: SmartLab

X-ray source: Cu-Kα

Scan axis: 2θ/θ

Mode: Continuous

Measuring range: 2θ=5° to 70°

Step: 0.01°

Speed measurement time: 2θ=2°/minute

IS：1/2

RS:20.00mm

Output: 40kV-30mA

5.Particle size distribution

To 0.1 g of crystals, 0.1 g of water as a dispersion solvent and one drop of a dispersant (neutral detergent) were added and mixed, and the resultant was put into a device and subjected to ultrasonic treatment (3 minutes) before measurement.

Device: Made by Shimadzu Corporation: SALD-2200

Measurement method: laser diffraction method

6.YI value (yellowness)

烷18.0g，並藉由以下條件測定所得到之1,4-二

烷溶液的YI值(黃色度)。 Dissolve 2.0 g of crystals in 1,4-bis with a purity of 99% by weight or more

18.0g of alkane, and the obtained 1,4-bis was measured under the following conditions

YI value (yellowness) of alkane solution.

Device: Colorimeter (made by Nippon Denshoku Industry Co., Ltd., ZE6000)

Usage tank: glass test tube (diameter 24mm)

烷本身的著色不會對測定值造成影響之方式，於事前測定1,4-二

烷的色相並進行校正(空白測定)。於實施此空白測定後，將樣本的測定值設為本發明之YI值(黃色度)。 Also, it is based on the 1,4-bis used in the determination.

In such a way that the coloring of alkane itself will not affect the measured value, 1,4-bis is measured in advance.

Alkane color and calibration (blank measurement). After performing this blank measurement, the measured value of the sample is set as the YI value (yellowness) of the present invention.

〈Synthesis example〉

Synthesis of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluorine

A 1-liter four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 76.3 g (0.423 mol) of 9-quinone, 907.0 g (4.24 mol) of the alcohol represented by chemical formula (3), and phosphorus were added. 13.7g of tungstic acid and 388.7g of toluene were reacted at a reaction temperature of 100°C and a pressure of 42kPa while removing the water produced by the reaction. The disappearance of the raw materials was confirmed by liquid chromatography analysis, and the reaction was considered to be completed. The reaction liquid was cooled to 80°C, and 339.1g of toluene, 26.69g of 15% sodium hydroxide aqueous solution, and 250g of distilled water were added to neutralize the reaction liquid, and then the water layer was removed after leaving to stand. Carry out 4 times of water washing operation of "add 250g of distilled water to the obtained oil layer, stir it and let it stand to remove the water layer". After removing low-boiling-point substances such as solvents and unreacted alcohols represented by the chemical formula (3) from the obtained oil layer by distillation, dissolve it with 1500 g of toluene. residue. The toluene solution was cooled to 25°C, and the precipitated crystals were filtered to obtain 232.0 g of the target toluene inclusion compound (purity measured by high-speed liquid chromatography analysis: 98.0%, containing 5 wt. of toluene). %).

<Reference example 1>

Into a 200 ml four-necked flask equipped with a thermometer, stirrer, and cooling tube, add 9,9-bis[4-( with a residual solvent of less than 0.1% by weight and a purity of 98.9% as measured by high-speed liquid chromatography analysis. 20g of 2-hydroxyethoxy)-3-phenylphenyl]benzoate and 20g of acetone were dissolved at 50°C. Then, the mixture was cooled to 25°C at a cooling rate of 10°C per hour, stirred for 15 hours, and then filtered. The obtained crystal was dried under reduced pressure of 1.2 kPa and in an environment of 30° C. for 2 hours to obtain 12.1 g of crystal (purity 99.0%). The residual solvent of this crystal was measured and found to be 1.7% by weight of acetone. Furthermore, the crystal was dried under the same conditions for 2 hours, but the acetone content did not change. In addition, as a result of differential thermal/thermogravimetric analysis (DTG) of this crystal, it was confirmed that the heat required to remove the included acetone was approximately 96 J/g. A graph showing this differential thermal/thermogravimetric analysis (DTG) curve is shown in Figure 1.

<Example 1>

(crystallization step)

Add 42g of the toluene clathrate obtained in the above "Synthesis Example" and 63.3g of acetone into a 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube, and dissolve them at 55°C. After maintaining the solution temperature at 55°C, 27.2g of distilled water was added dropwise with stirring, and then 0.1g of the seed crystal obtained in the above "Reference Example" was added, and stirring was continued at 55°C for 0.5 hours. Cool to 50°C at a cooling rate of 5°C per hour, maintain at 50°C for 2 hours with stirring, and then cool to 30°C at a cooling rate of 5°C per hour. The precipitated crystals are filtered to obtain crystals belonging to an acetone inclusion compound.

(drying step)

The obtained crystals belonging to the acetone clathrate were dried for 2 hours in an environment with a temperature of 110° C. and a pressure of 1.2 kPa, thereby obtaining 23.0 g of crystals that were not a clathrate.

(Analysis results)

For the crystals obtained in the drying step, it was confirmed that the purity measured by high-speed liquid chromatography analysis was 98.8%, and the remaining solvents measured by HS-GC analysis were 0.2% by weight of toluene and 0.02% by weight of acetone. %. The median diameter (D50) of the obtained crystals was 28.6 μm, and the mode diameter was 39.6 μm.

The graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 2, and the graph showing the differential thermal/thermogravimetric analysis (DTG) curve is shown in Figure 3. The main characteristics of powder X-ray Spectral peaks (those with relative integrated intensity exceeding 5%) are listed in Table 1.

From these analyses, it was found that the obtained crystal was a crystal mixture having two endothermic peaks of 162.1°C and 176.9°C measured by differential scanning calorimetry, and that the crystal mixture was not a clathrate.

In addition, the crystal after the above-mentioned crystallization step (before the drying step) was dried under a reduced pressure of 1.2 kPa and a temperature of 30°C for 2 hours, and in the same method as the reference example, it was confirmed that even if it was further dried with acetone There is no change in the content. Differential thermal/thermogravimetric analysis (DTG) was performed on the crystal from which only the attached solvent was removed. As a result, it was also confirmed that the heat required to remove the included solvent such as acetone was approximately 80 J/g. A graph showing this differential thermal/thermogravimetric analysis (DTG) curve is shown in Figure 4.

<Example 2>

(crystallization step)

Add 5g of toluene inclusion complex of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride, 18g of acetone, and 0.25g of toluene into a test tube with a stirrer. And dissolve at 50℃. While maintaining the solution temperature at 50°C, 5 g of distilled water was slowly added, and crystals precipitated during the addition. After adding the entire amount of distilled water, the entire mixture was cooled to 27° C. and stirred for 16 hours, and then the precipitated crystals were filtered. The obtained crystals were dried at 1.2 kPa and 30° C., and it was confirmed that the adhering solvent could be removed by the same method as in Example 1, and crystals belonging to an acetone inclusion compound could be obtained. Differential thermal/thermogravimetric analysis (DTG) was performed on the obtained crystals of the acetone clathrate, and it was confirmed that the heat required to remove the included acetone was approximately 57 J/g. A graph showing this differential thermal/thermogravimetric analysis (DTG) curve is shown in Figure 5.

(drying step)

The obtained crystals belonging to the acetone clathrate were dried for 2 hours in an environment with a temperature of 120° C. and a pressure of 1.2 kPa, and 2.7 g of crystals that were not a clathrate were obtained.

(Analysis results)

For the crystals obtained in the drying step, it was confirmed that the purity measured by high-speed liquid chromatography analysis was 98.6%, and the remaining solvents measured by HS-GC analysis were 0.09% by weight of toluene and 0.01% by weight of acetone. %, and is a crystalline mixture with two endothermic peaks of 160.2°C and 176.1°C measured by differential scanning calorimetry. A graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 6.

<Example 3>

(crystallization step)

Into a 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube, add 30 g of the toluene inclusion compound obtained in the above "Synthesis Example" and 61.2 g of acetone, and dissolve them at 55°C while maintaining the solution temperature at 55°C. After adding 30 g of distilled water dropwise while stirring, 0.1 g of the seed crystal obtained in the above "Reference Example" was added. While maintaining the solution temperature at 55°C, 10.8 g of distilled water was added dropwise with stirring, and stirring was continued for 1 hour. Then, the mixture was cooled to 50°C at a cooling rate of 10°C per hour, maintained at 50°C for 15 hours, and the precipitated crystals were filtered. The obtained crystal was dried under reduced pressure of 1.2 kPa and in an environment of 30° C. for 2 hours. It was confirmed that the adhering solvent could be removed by the same method as in Example 1, and crystals belonging to an acetone clathrate were obtained. Differential thermal/thermogravimetric analysis (DTG) of the obtained crystals of the acetone inclusion compound showed that the heat required to remove the included acetone was approximately 70 J/g. A graph showing this differential thermal/thermogravimetric analysis (DTG) curve is shown in Figure 7.

(drying step)

The obtained crystals of the clathrate were dried under a reduced pressure of 1.2 kPa and in an environment of 110° C. for 2 hours to obtain 17.8 g of crystals that were not a clathrate.

(Analysis results)

For the crystals obtained in the drying step, it was confirmed that the purity measured by high-speed liquid chromatography analysis was 98.7%, and the remaining solvents measured by HS-GC analysis were 0.2% by weight of toluene and 0.05% by weight of acetone. %, and is a crystalline mixture with two endothermic peaks of 160.5°C and 176.7°C measured by differential scanning calorimetry. The median diameter (D50) of the obtained crystals was 46.0 μm, and the mode diameter was 60.1 μm.

A graph showing the differential scanning calorimetry (DSC) curve of the obtained crystals is shown in Section 8 As shown in the figure, the main peaks of powder X-rays (those with relative integrated intensity exceeding 5%) are listed in Table 2.

<Comparative example 1>

Into a 200 ml four-necked flask equipped with a thermometer, a stirrer and a cooling tube, 15 g of the toluene inclusion compound obtained in the above "Synthesis Example" and 17 g of acetone were added and dissolved at 50°C. Then, cooling was performed at a cooling rate of 10°C per hour, and the crystal obtained in the above reference example was added as a seed crystal at 40°C. After cooling to 25°C at a cooling rate of 10°C per hour, the mixture was stirred for 15 hours and then filtered. The obtained crystal was subjected to a reduced pressure of 1.2 kPa 11.2 g of crystals (purity 98.5%) were obtained by drying in an environment of 110° C. for 2 hours. The residual solvent of this crystal was measured and found to be 2.6% by weight of toluene and 0.09% by weight of acetone. That is, the obtained crystal is a toluene inclusion compound.

<Comparative example 2>

Additional tests were conducted on the manufacturing method described in Example 1 of Patent Document 4 mentioned above.

Specifically, a 1-liter four-necked flask equipped with a mixer, a cooling tube, and a thermometer was replaced with nitrogen, and 75 g (0.149 mol) of 9,9'-bis(4-hydroxy-3-phenylphenyl)benzoate was added. , 1.7g of potassium carbonate, 30.05g of ethylene carbonate (0.341mol), 112.5g of toluene and 7.5g of methyltriglyme, heated to 110°C, and stirred at the same temperature for 16 hours, using high-speed liquid Phase chromatography (hereinafter referred to as HPLC) measurement was performed to confirm the disappearance of the raw materials.

Then, 3.07 g of water was added, and hydrolysis was performed at 100° C. for 5 hours.

After the obtained reaction liquid was cooled to 90°C, 113 g of water was added, and the mixture was stirred at 80 to 85°C for 30 minutes, and then the water layer was separated after letting it stand. After repeating the same water washing operation three times, the solvent was removed from the obtained organic solvent layer to obtain a concentrate. To the obtained concentrate, 92 g of toluene and 348 g of methanol were added to obtain a crystallization solution. The obtained crystallization solution was heated to 65°C and stirred at the same temperature for 1 hour to completely dissolve the crystals, and then cooled at 0.1°C per minute to precipitate the crystals at 50°C, and at the same temperature Stir for 2 hours. Then, after further cooling to 22°C, the mixture was filtered to obtain crystals.

The obtained crystals were dried under reduced pressure of 1.3 kPa at 55°C for 3 hours, and then A part of the crystal was analyzed by HS-GC. As a result, it was confirmed that the crystal contained 3.5% by weight of methanol, which was the solvent used in the crystallization step. Even if the drying was continued for 3 hours under the same conditions and analyzed, the methanol content was still 4% by weight and did not decrease. The amount of heat required to remove the included solvent from the crystal was measured using DTG, and the result was approximately 875 J/g. Under reduced pressure with an internal pressure of 1.3 kPa, the internal temperature of the crystal was raised to 90°C and further dried for 3 hours. Since the content of methanol is 0.02% by weight, drying is completed.

A graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the obtained crystal is shown in Figure 9, and each analysis value is shown below.

Weight of the crystals obtained: 77.9g (yield: 88%)

HPLC purity: 98.6%

Toluene content: 0.01% by weight

Methanol content: 0.02% by weight

From the results of Comparative Example 2, it was confirmed that approximately 900 J/g of energy is required to remove methanol from the methanol inclusion compound.

In addition, the median diameter (D50) of the obtained crystals was 18.5 μm, and the mode diameter was 21.2 μm.

Additional tests were conducted on the manufacturing methods described in Comparative Example 1 and Examples 8, 12, 17, 19, and 20 of the above-mentioned Patent Document 5.

<Reference example 2>

(Comparative Example 1 of Patent Document 5)

Substitute nitrogen into a 1-liter four-necked flask equipped with a stirrer, heating cooler and thermometer, and add 60g (0.119mol) of 9,9'-bis(4-hydroxy-3-phenylphenyl)quin and 1.2g of potassium carbonate. , 24.15g (0.274mol) of ethylene carbonate and 60g of toluene, and stirred at 110°C for 34 hours. Then, 4.86 g of water was added, and reaction (hydrolysis) was performed at 100° C. for 11 hours. After the obtained reaction liquid was cooled to 85°C, 30g of toluene and 102g of water were added, and the mixture was stirred at 80 to 85°C for 30 minutes, and then the water layer was separated after standing. After repeating the same water washing operation three times, water was removed from the obtained organic solvent layer under reflux using a Dean-Stark device, and crystals were precipitated at 75° C. by cooling. Stir at the same temperature for 2 hours. After further cooling to 26°C, the mixture was filtered to obtain crystals. The obtained crystal was dried at 110 to 112° C. for 12 hours under reduced pressure with an internal pressure of 1.1 kPa.

The obtained crystal was analyzed by the above method, and it was confirmed that the obtained crystal belonged to a toluene clathrate.

The analysis results of the obtained crystals are as follows.

Weight of crystals obtained: 68.5g

HPLC purity: 97.5%

Toluene (guest molecule) content: 4.46% by weight

<Comparative example 3>

(Example 8 of Patent Document 5: Isobutyl Ketone)

Add 5 g of the toluene clathrate crystals obtained in Reference Example 2 and 25 g of diisobutyl ketone into a test tube equipped with a stirrer, and stir at 100°C for 5 hours without cooling. to filter. Then, it was dried in a nitrogen stream for 2 hours.

A graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 10, and each analysis value is shown below. HPLC purity: 98.40%

Toluene (guest molecule) content: below detection limit (HS-GC)

Melting point: 192℃

Aerated bulk density: 0.31g/cm ³

In addition, the above loose overall density is based on data measured by a simple test in a test tube.

From the results of Comparative Example 3, it was confirmed that the crystal obtained in Example 8 of the above-mentioned Patent Document 5 is a high melting point crystal with a melting point of 192°C, and the bulk bulk density is also a relatively low 0.31 g/cm ³ .

<Comparative Example 4> (Example 12 of Patent Document 5: Heptane)

5 g of the toluene clathrate crystals obtained in Reference Example 2 and 25 g of heptane were added to a test tube equipped with a stirrer, stirred at 100° C. for 2 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.

A graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 11, and each analysis value is shown below.

HPLC purity: 98.74%

Toluene (guest molecule) content: below detection limit (HS-GC)

Melting point: 191℃

Overall loose density: 0.38g/cm ³

In addition, the above loose overall density is based on data measured by a simple test in a test tube.

From the results of Comparative Example 4, it was confirmed that the crystal obtained in Example 12 of Patent Document 5 is a high melting point crystal with a melting point of 191°C.

<Comparative Example 5> (Example 17 of Patent Document 5: dibutyl ether)

Add 5 g of the toluene clathrate crystals obtained in Reference Example 2 and 25 g of dibutyl ether into a test tube equipped with a stirrer, stir at 100° C. for 5 hours, and filter directly without cooling. Then, it was dried in a nitrogen stream for 2 hours.

A graph showing a differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 12, and each analysis value is shown below.

HPLC purity: 97.88%

Toluene (guest molecule) content: below detection limit (HS-GC)

Melting point: 192℃

Overall loose density: 0.35g/cm ³

In addition, the above loose overall density is based on data measured by a simple test in a test tube.

From the results of Comparative Example 5, it was confirmed that the crystal obtained in Example 17 of Patent Document 5 is a high melting point crystal with a melting point of 192°C.

<Comparative example 6>

(Example 19 of Patent Document 5: Acetonitrile)

Add 5 g of the toluene clathrate crystals obtained in Reference Example 2 and 10 g of acetonitrile into a test tube equipped with a stirrer, stir at 24° C. for 6 hours, and filter without cooling. Then, it was dried in a nitrogen stream for 2 hours.

A graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the obtained crystal is shown in Figure 13, and each analysis value is shown below. HPLC purity: 98.15%

Acetonitrile (guest molecule) content: 3.57% (HS-GC)

Overall loose density: 0.32g/cm ³

In addition, the above loose overall density is based on data measured by a simple test in a test tube.

From the results of Comparative Example 6, it was confirmed that approximately 200 J/g of energy must be consumed in order to remove acetonitrile from the acetonitrile inclusion compound.

<Comparative Example 7>

A 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 14.1 g of the toluene clathrate obtained in the above "Synthesis Example" (YI value 0.80), 60 g of methyl isobutyl ketone and heptane were added thereto. Add 24 g of alkane, raise the temperature to 100°C, and stir for 30 minutes to dissolve all the crystals. The obtained solution was cooled at a rate of 0.8°C per minute to precipitate crystals at 65°C. After stirring at the same temperature for 2 hours, the mixture was cooled to 20°C and filtered. The obtained crystals were dried at 90°C under reduced pressure of 1.3 kPa for 3 hours, and 10.6 g of crystals of the following quality were obtained.

HPLC purity: 99.3%

Residual toluene: 112ppm

Residual methyl isobutyl ketone: 1680ppm

Residual heptane: 321ppm

烷溶液) YI value: 1.26 (10%

alkane solution)

DSC melting endothermic maximum temperature: 171℃

<Example 4>

A 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 14.3 g of the toluene inclusion compound (YI value 0.80) obtained in the above "Synthesis Example" and 30.6 g of acetone were added to it, and dissolved at 55°C. Afterwards, 15 g of distilled water was added dropwise with stirring while maintaining the solution temperature at 55°C, and then 0.1 g of the seed crystal obtained in the above "Reference Example" was added. While maintaining the solution temperature at 55°C, 5.4 g of distilled water was added dropwise with stirring, and stirring was continued for 1 hour. Then, the mixture was cooled to 50°C at a rate of 10°C per hour, maintained at 50°C for 15 hours, and the precipitated crystals were filtered. The obtained crystal was dried at 100° C. for 4 hours under reduced pressure of 1.3 kPa, and 9.9 g of crystal of the following quality was obtained.

HPLC purity: 99.1%

Residual toluene: 0.10% by weight

Residual acetone: 0.01% by weight

烷溶液) YI value: 0.43 (10%

alkane solution)

According to the endothermic spectrum peak measured by DSC: 162℃/176℃

As shown in the above-mentioned "Comparative Example 7", the method described in the above-mentioned Patent Document 5 cannot improve the hue of the crystal. However, as shown in the "Example 4", it is confirmed that the method according to the present invention can also significantly improve the hue. Improves the hue of the resulting crystal.

Additional tests were conducted on the manufacturing methods described in Examples 1 and 2 of Patent Document 6 mentioned above.

<Comparative example 8>

(Example 1 of Patent Document 6)

A 1-liter four-necked flask equipped with a thermometer, stirrer, and cooling tube was replaced with nitrogen, and 18.0 g (0.1 mol) of 9-quinone and 53.5 g (0.25 mol) of 2-[(2-phenyl)phenoxy]ethanol were added. Mol), 1 g of 3-mercaptopropionic acid, and 60 mL of toluene. After dissolving at 65°C, 25 mL of 98% sulfuric acid was added dropwise over 1 hour. The reaction was then stirred at 65°C for 6 hours. After the reaction is completed, sodium hydroxide solution is added to neutralize, and then 100 g of toluene and 50 g of water are added and stirred, and then the water layer is removed after letting it stand. The operation of "adding 60 g of water to the obtained organic layer, stirring, leaving it to stand, and then removing the water layer" was performed four times.

The washed organic layer was cooled and crystallized at 10°C/hour, stirred at 25°C for 15 hours, and then filtered to obtain 9,9-bis[3-phenyl-4-(2-hydroxyethoxy The crude product of phenyl]fluorine.

20.2 g of this crude product was dissolved in 60.6 g of toluene, then cooled and crystallized, and filtered at 25° C. to obtain 9,9-bis[3-phenyl-4-(2-hydroxyethoxy)phenyl. ] The crystallization of Fu. Then, it was dried at 80° C. and 1.3 kPa for 6 hours to obtain 11 g of crystals (yield 19.0%).

The crystal was analyzed by HPLC and the purity was 92.8%.

A graph showing the differential thermal/thermogravimetric analysis (DTG) curve of the obtained crystal is shown in Figure 14.

According to Figure 14, it can be seen that the crystal obtained by Example 1 of Patent Document 6 is a toluene clathrate because the weight of the crystal decreases at a temperature above the melting point.

<Comparative Example 9>

(Example 2 of Patent Document 6)

After dissolving 10 g of the crystals of Comparative Example 8 with 60 g of ethanol, the solution was cooled, crystallized, and filtered at 25° C. to obtain crystals. After drying at 25° C. and 1.3 kPa for 3 hours, analysis was performed by HS-GC. The result was that the ethanol content was 6.0% by weight. Differential thermal/thermogravimetric analysis (DTG) was performed on this crystal, and it was confirmed that the heat required to remove included ethanol was approximately 147 J/g. A graph showing the differential thermal/thermogravimetric analysis (DTG) curve of this crystal is shown in Figure 15.

Furthermore, this crystal was dried at 80°C and 1.3 kPa for 6 hours. As a result, 6.9 g of crystals with an ethanol content of 0.14% by weight were obtained (yield 69%). A graph showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in Figure 16, and each analysis value is shown below.

HPLC purity: 94.5%

Ethanol content: 0.14% by weight (HS-GC)

Toluene content: below detection limit (HS-GC)

Melting point: 132℃

Overall loose density: 0.33g/cm ³

In addition, the above loose overall density is based on data measured by a simple test in a test tube. In addition, the HPLC purity is lower than the value described in Patent Document 6. It is believed that the reaction conditions are not completely consistent because details such as the sulfuric acid dropping temperature are not explained in Example 6.

In addition, the median diameter (D50) of the obtained crystals was 20.7 μm, and the mode diameter was 26.1 μm. Compared with the crystal mixture of the present invention, the particle size of the crystals obtained is extremely fine, and compared with the crystals obtained from the ethanol clathrate in "Comparative Example 2" above, no improvement in fluidity was confirmed. .

From the results of Comparative Example 9, it was confirmed that approximately 150 J/g of energy is required to remove ethanol from the ethanol clathrate. In addition, the melting point of the crystal after removing ethanol from the clathrate is 132°C.

Claims (5)

A crystalline mixture of 9,9-bis[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoride having at least 1 basis for differential scanning in a temperature range of 157°C above and 163°C below Endothermic peaks measured by thermal analysis, and having at least one endothermic peak in the temperature range of 176°C to 179°C. The crystal mixture as described in item 1 of the patent application, wherein each of the crystal mixture is not a clathrate. The crystalline mixture described in item 1 of the patent application is based on the powder X-ray diffraction pattern obtained by using Cu-Kα rays at diffraction angles 2θ=7.5±0.2°, 11.1±0.2°, and 17.6±0.2 °, 19.1±0.2°, 20.5±0.2° and 21.1±0.2° have spectral peaks. A method for manufacturing a crystal mixture described in any one of items 1 to 3 of the patent application, which includes the step of crystallizing using a mixed solvent of acetone and water. The manufacturing method described in item 4 of the patent application further includes the step of drying the crystals obtained by crystallization at a temperature above 45°C and below the melting point.

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